Laboratory work for the coming year will be devoted to studies of immunologic manipulation in cardiac transplantation and characterization of physiologic events during cardiac allograft rejection. Although markedly depressed immunocompetence is present in patients following total lymph node irradiation for treatment of malignancies, a similar regimen of nodal irradiation in dogs followed within several days by cardiac allografting results in an accelerated form of rejection rather than the anticipated prolongation of graft survival. Studies are planned to elucidate the mechanism of this form of accelerated rejection and to determine the time interval after nodal irradiation during which this phenomenon occurs. The efficacy of combining standard immunosuppressive drugs with total nodal irradiation will then be evaluated. We have previously shown that total myocardial blood flow is reduced and that the ratio of subendocardial to subepicardial myocardial flow is also diminished during an episode of acute rejection in the orthotopic canine cardiac allograft. The reversibility of these changes with high dose immunosuppressive therapy will be evaluated in an attempt to determine when irreversible vascular damage occurs in the rejection process. Study will continue on the mechanism of chicken antirat lymphocyte globulin (CARLG). Our current hypothesis is that this agent acts at least in part by binding to donor histocompatibility antigens with the antigen antibody complex functioning as an immunoregulatory signal. Finally, we will initiate a study of cardiac heterotransplantation utilizing the rabbit heart engrafted into the cervical position in the dog. The hyperacute rejection which occurs in this discordant xenograft system will be characterized and techniques involving masking of donor antigens for control of this reaction will be evaluated. BIBLIOGRAPHIC REFERENCES: Schroeder, J.S., Rider, A.K., Stinson, E.B., Shumway, N.E.: Cardiac transplantation: review of seven years' experience. Transplant. Proc. 8:5, 1976. Griepp, R.B., Stinson, E.B. and Shumway, N.E.: Transplantation of the Heart. IN SURGERY ANNUAL, L.M.Nyhus (ed.), Appleton-Century-Crofts, Meredith Corp., New York, 1976.